Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells #MMPMID27609109
Cho WK; Shin SW; Kim SY; Hong CW; Choi C; Park W; Noh JM
Radiat Oncol J 2016[Sep]; 34 (3): 223-229 PMID27609109show ga
PURPOSE: This study is to investigate the effect of captopril when combined with irradiation. MATERIALS AND METHODS: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF-1alpha) of tumor was evaluated by immunohistochemical (IHC) staining. RESULTS: The mean tumor volumes (+/-standard error) at the 15th day after randomization were 1,382.0 (+/-201.2) mm(3) (group 1), 559.9 (+/-67.8) mm(3) (group 3), and 370.5 (+/- 48.1) mm(3) (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and HIF-1alpha positivity in tumor cells were decreased when treated with captopril. CONCLUSION: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.
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Radiat+Oncol+J 2016 ; 34 (3): 223-229
